Translational gastroenterology and hepatology最新文献

{"title":"Eosinophilic and mastocytic gastrointestinal diseases: current knowledge and controversy in histopathologic diagnosis.","authors":"Weibo Yu, Hanlin L Wang","doi":"10.21037/tgh-2025-146","DOIUrl":"https://doi.org/10.21037/tgh-2025-146","url":null,"abstract":"<p><p>Eosinophilic and mastocytic gastrointestinal (GI) diseases represent a spectrum of immune-mediated inflammatory disorders characterized by abnormal accumulation of eosinophils or mast cells in the GI tract. This review summarizes current knowledge on epidemiology, pathogenesis, histopathologic features, diagnostic challenges, and ongoing controversies across three major domains: eosinophilic esophagitis (EoE), non-EoE eosinophilic gastrointestinal diseases (EGID), and mastocytic GI diseases. Although these entities are increasingly recognized in clinical practice, their diagnosis remains challenging because clinical manifestations are often nonspecific and overlap with other inflammatory and functional GI disorders. Consequently, substantial uncertainties persist regarding diagnostic criteria and clinical relevance of certain histologic patterns. For non-EoE EGIDs, histologic diagnosis is particularly complicated by wide regional variation in normal eosinophil densities, the lack of universally accepted diagnostic cutoffs in adults, and limited correlation between tissue eosinophil burden and symptom severity. In mastocytic GI diseases, additional challenges include distinguishing reactive mast cell hyperplasia from clonal mastocytosis and interpreting proposed entities such as mastocytic enterocolitis, whose clinical significance remains controversial. Given these limitations, histopathologic evaluation of GI biopsies plays a central role in disease recognition and classification. This review emphasizes practical aspects of tissue interpretation, including site-specific reference ranges, proposed diagnostic thresholds, characteristic morphologic patterns, ancillary immunohistochemical and molecular studies, and common interpretive pitfalls encountered in routine practice. Recognizing these diseases ultimately requires careful clinicopathologic correlation, integrating histologic findings with clinical, endoscopic, and molecular data. Improved standardization of diagnostic criteria and clearer definition of histologic thresholds remain critical unmet needs for both pathologists and clinicians managing these complex disorders.</p>","PeriodicalId":94362,"journal":{"name":"Translational gastroenterology and hepatology","volume":"11 ","pages":"48"},"PeriodicalIF":2.5,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13066351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147680057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences and trends in worldwide clinical guidelines for <i>Helicobacter pylori</i> infection.","authors":"Mitsushige Sugimoto, Masaki Murata","doi":"10.21037/tgh-2025-159","DOIUrl":"https://doi.org/10.21037/tgh-2025-159","url":null,"abstract":"<p><p><i>Helicobacter pylori</i> (<i>H. pylori</i>) infection is the most common human infection worldwide, affecting approximately 40-60% of the global population. Eradication therapy is the primary treatment for preventing the development of peptic ulcers and gastric cancer. <i>H. pylori</i> eradication regimens should be selected based on those expected to achieve the highest eradication rates at treatment initiation in the area/country. In general, eradication regimens capable of achieving eradication rates of ≥90% are considered optimal. The success or failure of eradication therapy depends on several factors, including susceptibility to the antimicrobial agents used, inadequate acid inhibition during therapy, and poor medication adherence. Clinical guidelines and consensus reports for <i>H. pylori</i> infections are periodically updated worldwide. Recommended eradication regimens evolve in response to changing regional antibiotic resistance patterns, the introduction of new antimicrobial agents and acid-suppressing therapies, and regional insurance system-related challenges. Therefore, eradication regimens vary depending on the region covered by specific guidelines and consensus reports. This review aimed to explain regional differences in clinical guidelines and consensus reports for <i>H. pylori</i> infection, track their changes over time, and summarize future directions for eradication therapy.</p>","PeriodicalId":94362,"journal":{"name":"Translational gastroenterology and hepatology","volume":"11 ","pages":"47"},"PeriodicalIF":2.5,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13066358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147680047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence-based prediction of esophageal adenocarcinoma risk in Barrett's esophagus patients: a literature review.","authors":"Priyanka Ahuja, Manesh Kumar Gangwani, Neha Ahuja, Faisal Kamal, Yash Shah, Hassam Ali, Muhammad Aziz, Meer Akbar Ali, Sumant Inamdar","doi":"10.21037/tgh-25-92","DOIUrl":"https://doi.org/10.21037/tgh-25-92","url":null,"abstract":"<p><strong>Background and objective: </strong>Barrett's esophagus (BE) is the principal precursor lesion for esophageal adenocarcinoma (EAC), a malignancy with rising incidence and poor survival when diagnosed at advanced stages. Current screening and surveillance strategies rely on endoscopy and random biopsies, which are invasive, resource-intensive, and prone to sampling error. Artificial intelligence (AI) has emerged as a promising tool to enhance early detection, risk stratification, and surveillance efficiency in BE. This narrative review summarizes contemporary AI applications in BE management, evaluates their diagnostic and predictive performance, and discusses barriers to clinical adoption.</p><p><strong>Methods: </strong>A narrative literature review was conducted using PubMed, Embase, Scopus, Web of Science, and Cochrane. ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) were checked for ongoing trials and Good Scholar was used for citation chasing to identify peer-reviewed studies up to June 2025. Eligible studies evaluated AI-based approaches for BE screening, dysplasia detection, risk prediction, or surveillance optimization using vision-based or non-vision-based models.</p><p><strong>Key content and findings: </strong>Vision-aided AI systems, particularly convolutional neural networks applied to high-definition white-light endoscopy and image-enhanced endoscopy, demonstrate sensitivities approaching 90% for dysplasia and early EAC detection. Non-vision-based models leveraging electronic health records, biomarkers, and histopathology achieve area under the receiver operating characteristic curve (AUROC) values up to 0.84 for predicting BE or EAC risk. Multimodal approaches integrating clinical, endoscopic, and molecular data show promise for personalized surveillance strategies. However, challenges remain, including limited external validation, algorithm transparency, data bias, workflow integration, and cost considerations.</p><p><strong>Conclusions: </strong>AI has the potential to transform BE care by improving early detection and enabling risk-adapted surveillance. Multicenter validation, explainable models, and cost-effectiveness analyses are essential before widespread clinical implementation.</p>","PeriodicalId":94362,"journal":{"name":"Translational gastroenterology and hepatology","volume":"11 ","pages":"50"},"PeriodicalIF":2.5,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13066356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging KRAS G12D inhibitor in the treatment of digestive system tumors: opportunities and challenges.","authors":"Xiaohan Wu, Hiromitsu Hayashi, Takumi Tanizaki, Yuxuan Sun, Masaaki Iwatsuki","doi":"10.21037/tgh-25-124","DOIUrl":"https://doi.org/10.21037/tgh-25-124","url":null,"abstract":"<p><p>The <i>KRAS</i> G12D mutation, defined by substitution of glycine with aspartic acid at codon 12 within the GTP-binding region of the <i>KRAS</i> gene, occurs with particularly high prevalence in digestive system malignancies, especially pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC). Oncogenic <i>KRAS</i> variants drive persistent activation of downstream signaling cascades, including the MAPK and PI3K pathways, thereby circumventing upstream regulation and fueling tumor initiation, progression, and therapeutic resistance. Because of its high intrinsic affinity for GTP/GDP and the lack of a readily accessible binding pocket, KRAS was long considered a difficult therapeutic target. The emergence of MRTX1133, a highly selective, noncovalent inhibitor that specifically binds the Switch II pocket of KRAS G12D, represents a major advance in precision oncology. By engaging this unique pocket, MRTX1133 effectively blocks effector interactions and potently suppresses MAPK and PI3K signaling. Preclinical investigations have revealed that MRTX1133 elicits strong antitumor responses in <i>KRAS</i> G12D mutant PDAC and CRC models, including pronounced tumor regression, enhanced apoptosis, and inhibition of metastatic features. Nonetheless, as observed with other targeted agents, resistance can arise through feedback activation of receptor tyrosine kinases, reactivation of parallel signaling pathways, metabolic reprogramming, and tumor microenvironmental influences. These findings underscore the importance of combination therapeutic approaches in overcoming resistance. This review summarizes current evidence on the mechanisms of action, resistance pathways, and potential combination strategies of MRTX1133 in digestive system cancers, and discusses its translational relevance and clinical implications for <i>KRAS</i> G12D mutant malignancies.</p>","PeriodicalId":94362,"journal":{"name":"Translational gastroenterology and hepatology","volume":"11 ","pages":"49"},"PeriodicalIF":2.5,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13066353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147680096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence-assisted detection of internal openings in anal fistulas using endorectal ultrasound: a YOLOv11-based diagnostic system.","authors":"Xu Wang, Xingyue Ma, Xiaoqian Tong, Zhigang Luo, Ting Liu, Jiaqi Yang, Xiaotian Liu, Yanting Wen","doi":"10.21037/tgh-25-122","DOIUrl":"https://doi.org/10.21037/tgh-25-122","url":null,"abstract":"<p><strong>Background: </strong>Accurate and efficient detection of internal openings (IO) of anal fistulas (AF) in endorectal ultrasound (ERUS) images is crucial for diagnosis and treatment planning. This study aimed to develop an artificial intelligence (AI) system to automatically identify these anatomical landmarks in real time, thereby improving diagnostic efficiency.</p><p><strong>Methods: </strong>An AI system based on the YOLOv11 architecture (YOLOv11n model) was constructed. The model was trained and evaluated using a dataset consisting of 238 ERUS cases from The Fifth People's Hospital of Chengdu. The system's performance was assessed using conventional object detection metrics, including precision, recall, and mean average precision (mAP) at various intersection-over-union (IoU) thresholds.</p><p><strong>Results: </strong>The proposed YOLOv11n model demonstrated excellent performance in detecting IO of AF. The results showed precision of 0.925, recall of 1.0, mAP of 0.99 at an IoU threshold of 0.5, and mAP of 0.602 across IoU thresholds from 0.50 to 0.95. These findings highlight the model's robustness, reliability, and accuracy in rapidly analyzing ERUS images.</p><p><strong>Conclusions: </strong>Utilizing the YOLOv11 architecture, this AI system enables real-time, precise identification of IO of AF in ERUS images, significantly enhancing diagnostic efficiency. The system's outstanding performance offers potential for standardized training for radiologists and colorectal surgeons, effectively integrating AI advancements with clinical educational needs.</p>","PeriodicalId":94362,"journal":{"name":"Translational gastroenterology and hepatology","volume":"11 ","pages":"46"},"PeriodicalIF":2.5,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13066350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Body mass index has no impact on complications and mortality for patients with stage IV pancreatic ductal adenocarcinoma.","authors":"Ren Bryant, Hannah Darnell, Megan Hall, Kelsey Karnik, Kristen McQuerry, Ruben R Plentz","doi":"10.21037/tgh-2025-160","DOIUrl":"https://doi.org/10.21037/tgh-2025-160","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of United States (USA) cancer death. Overweight and obesity developing into a growing global medical and socio-economic problem, affecting approximately 42% of adults in the USA population. The aim of our analysis was to evaluate the influence of overweight and obesity on complications and clinical outcome in patients with stage IV PDAC.</p><p><strong>Methods: </strong>We retrospectively reviewed electronic health records of patients diagnosed with stage IV PDAC (n=162) who followed with the University of Kentucky from January 2017-October 2024. Comparisons were based on the body mass index (BMI): low BMI (BMI <25 kg/m²) <i>vs</i>. high BMI (BMI ≥25 kg/m²). Associations between groups were analysed by Chi Square method, <i>t</i>-tests, and if needed, Fischer exact test.</p><p><strong>Results: </strong>Smoking status showed significant higher current and former smokers in the high BMI group (P=0.005). No significant difference was seen for lab parameter. Hypertension was the most frequent comorbidity (n=101). Type 2 diabetes was significantly more prevalent in the high BMI group (55.8% <i>vs</i>. 38.2%; P=0.03). FOLFIRINOX (fluorouracil, leucovorin, irinotecan, oxaliplatin) therapy was more frequent in the high BMI group (44.2% <i>vs</i>. 34.2%). No significant differences were observed between the groups in terms of chemotherapy lines or complications, including thrombosis, infection, endoscopic interventions and gastrointestinal (GI) bleeding. No difference for mortality was observed.</p><p><strong>Conclusions: </strong>Our data clearly show that neither higher nor lower BMI is a contraindication for systemic chemotherapy of stage IV PDAC. Complications and mortality were not different between the groups. However, hospice referrals were more frequent in patients with low BMI, which may be from cognitive biases due to the more cachectic appearing phenotype.</p>","PeriodicalId":94362,"journal":{"name":"Translational gastroenterology and hepatology","volume":"11 ","pages":"43"},"PeriodicalIF":2.5,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13066355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conjugated bilirubin in chronic liver disease: an underutilised prognostic biomarker?-a narrative review.","authors":"Elise Fawcett, Aloysious D Aravinthan","doi":"10.21037/tgh-25-132","DOIUrl":"https://doi.org/10.21037/tgh-25-132","url":null,"abstract":"<p><strong>Background and objective: </strong>Chronic liver disease (CLD) is a major global health burden, often progressing to cirrhosis, decompensation, and hepatocellular carcinoma. Prognostic models typically rely on serum total bilirubin. However, recent evidence suggests that conjugated bilirubin (C-BIL) may offer superior prognostic utility in assessing disease severity and outcomes in CLD. This narrative review aims to examine the emerging evidence supporting C-BIL as a prognostic and disease stratification biomarker across various clinical contexts, where it has demonstrated enhanced predictive accuracy over traditional measures.</p><p><strong>Methods: </strong>A comprehensive, non-systematic review of the published literature was undertaken using major bibliographic databases and predefined keywords. Relevant studies were selected based on the following criteria: English-language publications, studies conducted in human populations, and articles with clear clinical applicability. Emphasis was placed on studies evaluating C-BIL in prognostic or disease-stratification contexts within CLD.</p><p><strong>Key content and findings: </strong>Emerging evidence indicates that incorporation of C-BIL into clinical prognostic models may enhance risk stratification and support more informed clinical decision-making in CLD. Elevated C-BIL appears to reflect impaired hepatocellular excretory function and fibrosis-related biliary obstruction. In addition, recent studies suggest that hepatocyte senescence may represent an additional, biologically plausible mechanism underpinning its prognostic relevance.</p><p><strong>Conclusions: </strong>This review highlights the potential clinical utility of C-BIL as a prognostic biomarker in CLD. While existing evidence supports its role in disease stratification and outcome prediction, further prospective validation and mechanistic studies are required before C-BIL can be adopted as a standard component of prognostic assessment in CLD.</p>","PeriodicalId":94362,"journal":{"name":"Translational gastroenterology and hepatology","volume":"11 ","pages":"51"},"PeriodicalIF":2.5,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13066352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147680013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of preoperative biliary drainage on surgical risk in pancreaticoduodenectomy for resectable periampullary tumors.","authors":"Huajun Lin, Boyu Deng, Chenglin Xin, Peixin Li, Ying Jian, Xiaoya Yu, Tianyi Wang, Dong Wang","doi":"10.21037/tgh-2025-161","DOIUrl":"https://doi.org/10.21037/tgh-2025-161","url":null,"abstract":"<p><strong>Background: </strong>Pancreaticoduodenectomy (PD), as a challenging surgical procedure, is associated with considerable morbidity and mortality rates. Currently, the impact of preoperative biliary drainage (PBD) on the surgical risk of PD remains controversial. Therefore, we conducted a retrospective cohort study to analyze factors influencing the surgical risk of PD and to evaluate the role of biliary drainage therein.</p><p><strong>Methods: </strong>A retrospective analysis was performed on the clinical data of 354 patients with periampullary malignancies who underwent PD at Beijing Friendship Hospital, Capital Medical University, between June 2017 and October 2022. Through comprehensive scoring based on surgical approach, operative time, and intraoperative blood loss, we derived surgical risk scores and stratified patients into high-risk and low-risk groups. Variables including patient history, preoperative procedures, and laboratory and imaging findings were included in least absolute shrinkage and selection operator (LASSO) regression to identify variables at the optimal lambda value. These variables were then incorporated into binary multivariate logistic regression to analyze factors influencing the surgical risk of PD. Furthermore, we analyzed influencing factors specifically in patients who underwent PBD to identify risk factors affecting surgical risk in this subgroup.</p><p><strong>Results: </strong>A total of 354 patients were included in this study, with 195 cases stratified into the low-risk group and 159 cases assigned to the high-risk group. Among all 354 enrolled patients, 184 did not undergo PBD, while 170 underwent PBD. Analysis revealed that the biliary drainage group had a higher surgical risk compared to the non-drainage group [odds ratio (OR): 1.615; 95% confidence interval (CI): 1.020-2.556, P=0.04]. Further analysis of the impact of different biliary drainage methods on surgical difficulty showed that, among patients who underwent PBD, retrograde drainage was a risk factor for surgical risk (OR: 2.032; 95% CI: 1.016-4.064, P=0.045).</p><p><strong>Conclusions: </strong>PBD was identified as an independent risk factor for elevated surgical risk in PD. Among patients undergoing biliary drainage, retrograde drainage, compared to antegrade drainage, is an independent risk factor for surgical risk.</p>","PeriodicalId":94362,"journal":{"name":"Translational gastroenterology and hepatology","volume":"11 ","pages":"42"},"PeriodicalIF":2.5,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13066348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147680060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular and regional characterization of colorectal polyps: insights from proteomics, phosphoproteomics, and immune profiling.","authors":"Thomas M Attard, Shawn D St Peter, Alexander Kats, Doug R Lagemann, Caitlin E Lawson, Badal C Roy, Kafayat Yusuf, Lisa Harvey, Payel Bhanja, Rishi Man Chugh, Subhrajit Saha, Michael P Washburn, Shahid Umar","doi":"10.21037/tgh-2025-138","DOIUrl":"https://doi.org/10.21037/tgh-2025-138","url":null,"abstract":"<p><strong>Background: </strong>Familial adenomatous polyposis (FAP) is an inherited predisposition to colorectal cancer and characterized by profuse colorectal adenomas starting from the second decade of life. Regional (left <i>vs.</i> right) differences in the colonic microbiologic and immunologic microenvironment may impact adenoma evolution but are poorly understood. We aimed to characterize regional molecular, microbial, DNA damage, and immune differences in pediatric FAP polyps to test the hypothesis that polyps in pediatric FAP exhibit distinct regional and molecular features that contribute to differential growth and genomic instability.</p><p><strong>Methods: </strong>Colonic polyps and adjacent non-polyp mucosa were harvested from pediatric FAP patients undergoing colonoscopy. Tandem mass tag-based proteomic and phosphoproteomic profiling was performed and were followed by functional assays including colony formation, spheroid growth, and patient-derived organoid culture. γH2AX staining was used to quantify induction of DNA double-strand breaks (DSBs) in HCT116 colon cancer cells cultured in <i>Fusobacterium nucleatum</i> conditioned media (<i>Fn</i>CM). Immunohistochemistry and immunofluorescence were used to assess ATR, CDK4, γH2AX, and oxidative damage (8-OxoG). Immune profiling was performed by flow cytometry, focusing on CD103⁺ tissue-resident memory T cells (TRMs).</p><p><strong>Results: </strong>Right-sided polyps exhibited increased ATR and CDK4 expression compared with left-sided lesions and adjacent mucosa. <i>Fn</i>CM exposure induced a marked increase in γH2AX staining in HCT116 cells, consistent with our <i>in vivo</i> findings of elevated DSB burden in proximal versus distal FAP polyps. Biofilm enrichment and higher microbial staining were observed in right-sided lesions, whereas distal polyps were enriched with CD103⁺ TRM populations. Pharmacologic inhibition of ATR or CDK4 significantly suppressed both colony formation and spheroid growth. Organoids derived from proximal colon polyps exhibited accelerated growth and crypt budding, with higher expression of stemness markers (CD44, CD133, Lgr5, BMI-1) compared with distal polyps.</p><p><strong>Conclusions: </strong>Integrated proteomic, phosphoproteomic, and immune-microbiome profiling reveals regional heterogeneity of adenomas in pediatric FAP. Right compared to left sided polyps harbor greater DNA damage, elevated ATR/CDK4 kinase activity, reduced immune surveillance, and increased stem-like growth. These findings identify ATR and CDK4 as potential therapeutic targets and suggest that regional microenvironmental differences can impact chemoprevention strategies in pediatric FAP.</p>","PeriodicalId":94362,"journal":{"name":"Translational gastroenterology and hepatology","volume":"11 ","pages":"44"},"PeriodicalIF":2.5,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13066361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147680092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the association between gut microbiota metabolites and hepatocellular carcinoma via network pharmacology.","authors":"Jianxu Yuan, Yunyun Zhang, Ji Zheng, Shengjie Yu","doi":"10.21037/tgh-2025-143","DOIUrl":"https://doi.org/10.21037/tgh-2025-143","url":null,"abstract":"<p><strong>Background: </strong>Gut microbiota plays a pivotal role in human homeostasis and health. This study adopted network pharmacology to clarify the metabolic transformation of gut microbiota metabolites and their molecular mechanisms in hepatocellular carcinoma (HCC) pathogenesis, aiming to unravel the complex crosstalk between gut microbiota, metabolites, and key genes.</p><p><strong>Methods: </strong>Gut microbiota metabolites and their associated genes were retrieved from the gutMGene database. Metabolite target genes were predicted using the SEA and STP databases, while HCC-related genes were compiled from GeneCards, OMIM, and CTD. Intersection analysis identified key genes mediating metabolite-regulated HCC progression. Core genes were screened via a protein-protein interaction (PPI) network, and comprehensive Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were further performed. A \"microbiota-substrate-metabolite-target\" network was constructed, and metabolites were evaluated for drug-likeness and toxicity to identify therapeutic candidates.</p><p><strong>Results: </strong>A total of 52 key genes involved in the gut microbiota-HCC interaction were screened, with <i>IL6</i>, <i>TNF</i>, and <i>TP53</i> as hub genes. The Microbial Substrate Metabolite Target (M-S-M-T) network showed these hubs regulate HCC via 8 metabolites, 5 substrates, and 20 microorganisms. GO enrichment analysis indicated these key genes were mainly enriched in bacterial molecule response, membrane rafts, and DNA-binding transcription factor binding. KEGG enrichment analysis showed they were primarily associated with PI3K-Akt, MAPK, and Toll-like receptor signaling pathways. Three metabolites exhibited HCC therapeutic potential.</p><p><strong>Conclusions: </strong>Gut microbiota metabolites may exert regulatory effects on HCC mainly by targeting core genes. Targeting these genes in the regulatory network may offer a novel multidimensional therapeutic approach for HCC, and the identified metabolites could act as potential therapeutic candidates for HCC.</p>","PeriodicalId":94362,"journal":{"name":"Translational gastroenterology and hepatology","volume":"11 ","pages":"41"},"PeriodicalIF":2.5,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13066360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147680138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}